Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 25 patients with metastatic renal cancer were treated on a phase II protocol with 5 days of continuous-infusion fluorodeoxyuridine (FUDR), (0.1 mg/kg daily) together with high-dose oral leucovorin (100 mg 4 h) and daily x6 high-dose interferon-alpha 2b (30 x 10(6) IU/m2). Despite the good performance status of the patients and the inclusion of 14 previously untreated patients in the cohort, no response was observed among the 20 evaluable patients. Toxicities included high fever, moderate anemia, transient leukopenia, transient and mild elevations of transaminases, and moderate to severe nausea, vomiting, diarrhea, and mucositis. There were also two episodes each of confusion, fluid retention, and pancreatitis and one episode of increased creatinine levels. During the study three deaths occurred, two of which were possibly therapy-related. Despite previous reports of activity of FUDR in metastatic renal cancer, the present regimen cannot be recommended.
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PMID:Continuous-infusion fluorodeoxyuridine with leucovorin and high-dose interferon: a phase II study in metastatic renal-cell cancer. 146 58

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.
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PMID:A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 151 22

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

Carbetimer (carboxyimamidate) is a low molecular weight derivative of ethylene/maleic anhydride polymer. This compound has demonstrated antitumor activity against several animal models with a daily x 5 schedule appearing most effective. A phase I clinical study of the daily x 5 schedule repeated every 28 days was therefore performed. Forty-one evaluable patients received 66 evaluable cycles of Carbetimer at daily doses ranging from 100-11,000 mg/m2. Hypercalcemia was the dose limiting toxicity with both patients at the 11,000 mg/m2 daily dose level and one patient who received 6 cycles of drug at the 4200 mg/m2 dose level developing severe hypercalcemia not explained by the underlying malignancy. Mild nausea, concentration and rate dependent arm pain at the site of infusion, proteinuria, and coagulopathy were also seen. Calcium balance studies revealed hypercalciuria, suggesting increased mobilization of calcium rather than renal retention. In vitro coagulation studies revealed concentration dependent prolongation of the partial thromboplastin time and thrombin time. No complete or partial responses were seen. However mixed response or biochemical response (reduction in serum lactic dehydrogenase) were seen in 5 patients with melanoma or renal cancer. Due to unacceptable toxicity at the 11,000 mg/m2 daily dose level, Carbetimer 8500 mg/m2 is the recommended dose for a 5-day treatment schedule every 28 days. Special attention should be directed toward possible activity against melanoma and renal cancer.
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PMID:Phase I trial of a 5-day course of carbetimer. 238 16

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
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PMID:A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. 238 96

High-dose interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells has been reported to have activity in certain solid tumors, but toxicity has usually required hospitalization for administration. The purpose of this trial was to determine the antineoplastic effect and toxicity of IL-2 administered at a lower dose in an outpatient setting. Eligibility criteria included measurable disease, Karnofsky performance greater than or equal to 70%, age greater than 18 years, and adequate bone marrow, renal, and hepatic function. The median age of 35 patients was 56 years (range, 20 to 75). Diagnoses included malignant lymphoma (ML), (nine patients), chronic lymphocytic leukemia (CLL) (eight), melanoma (eight), colorectal cancer (six), renal cancer (two), and breast cancer (two). The initial 18 patients were treated with 1 mg/m2 (3 x 10(6) U/m2 intravenous [IV] bolus) for five days every other week for a total of 4 treatment weeks (8 weeks total). The subsequent 17 patients were treated with 0.5 mg/m2 (1.5 x 10(6) U/m2). All patients were evaluable for toxicity, and 26 for tumor response. Toxicities included fatigue (71%), nausea (69%), hypotension (54%), fever (51%), chills (40%), weight gain (37%), pruritus or rash (31%), dyspnea (14%), azotemia (6%), confusion (6%), thrombocytopenia (6%), and myocardial infarction (3%). Four patients died from apparently unrelated causes within the first 2 weeks of treatment. Treatment was discontinued before the completion of 8 weeks of treatment because of progressive disease (12 patients), severe hypotension (three), azotemia (one), myocardial infarction (one), early death (four), and miscellaneous causes (two). IL-2 at 1 mg/m2 IV for five days is associated with moderate toxicity, but a dose of 0.5 mg/m2 is tolerable for outpatient administration. Three partial responses (PR) and one minor response (MR) lasting 1 to 17+ months have been observed in 12 patients with ML and CLL evaluable for response. One additional MR was observed in a patient with melanoma. IL-2 deserves further study in patients with ML and CLL.
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PMID:Phase II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. 278 39

The response of a mouse's foot to heat was studied. Transplanted syngeneic tumor, C3H mouse mammary carcinoma, was treated with irradiation and hyperthermia in a waterbath. The tumor did not disappear in any of the mice treated with radiotherapy with a dose of 20 Gy alone, but disappearance of the tumor was observed in 11 of 15 and 6 of 8 of the mice treated with combined therapy of irradiation and hyperthermia. There was a significant difference between these two groups. Synergistic effect was confirmed (P less than 0.001, P less than 0.005). Hyperthermia using Thermotron RF-8 was performed on 19 patients (5 bladder cancers, 3 uterine cancers, 3 rectal cancers, 4 soft tissue tumors, 2 oral cancers, 1 biliary tract cancer, 1 renal cancer) between April, 1986 and December, 1986. They were irradiated with a daily dose of 1.5-2.0 Gy, 5 times a week and hyperthermia was performed within 30 minutes after each irradiation once or twice a week. Intratumoral temperature was kept at 43 degrees C-45 degrees C. Temperature over 41 degrees C was maintained in most patients. Clinical response was assessed by tumor regression rates. Partial response a (PRa), defined as 80% or more regression in tumor volume, was obtained in 1 bladder cancer patient and PRb, defined as 50% to less than 80% regression, was obtained in another 5 patients. Side effects were observed in all patients including mild skin burn, nausea and diarrhea. Rectovaginal fistula developed in 1 patient. Combined radiotherapy and hyperthermia seems to be useful in advanced cancer patients.
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PMID:[Combined radiotherapy and local external hyperthermia in advanced cancer--animal experiment and clinical study]. 361 62

We have experienced a case of iodide mumps after CT examination with 100 ml of iopamidol. The patient was a 70-year-old woman with a history of right nephrectomy due to right renal cancer. She underwent CT examination to explore local recurrence and abdominal metastases including lymph node and liver metastases. Three hours after the CT examination, she complained of nausea, vomiting, facial flushing, bilateral jaw pain, and fever. The laboratory findings 12 hours after CT examination showed increased white blood cells and elevated serum amylase enzyme. Analysis of the amylase fraction showed that 86% originated from the salivary glands. She was admitted to the hospital, and the symptoms continued for four days, with decreasing severity. Anti-inflammatory therapy was performed, and the patient was discharged six days after the event.
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PMID:Iodide mumps after contrast enhanced CT with iopamidol: a case report. 756 8

Thirteen patients with metastatic renal cancer were treated in a phase II trial with interleukin-2, 21.6 million IU/m2 intravenously daily for five days on two consecutive weeks, starting 3 days after the administration of low dose cyclophosphamide 350 mg/m2 intravenously. Treatment cycles were repeated every 21 days. No responses were seen (95% Confidence Interval: 0-22%). The most common toxicities were fever, fatigue, hypotension, nausea/emesis, and myalgia/arthralgia. There were 11 episodes of Grade III toxicity including Grade III hypotension in 7 patients. Because of the significant toxicity and the lack of observed response, the study was discontinued. Cyclophosphamide and interleukin-2 at the dose and schedule used in this study has considerable toxicity and is unlikely to improve on response rates previously seen with other IL-2 based regimens in metastatic renal cancer.
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PMID:Phase II study of low dose cyclophosphamide and intravenous interleukin-2 in metastatic renal cancer. 796 Jun 3

Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 micrograms/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 micrograms/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 micrograms/m2. One complete response occurred in a patient with metastatic melanoma (duration > or = 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.
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PMID:Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma. 813 48


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